A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis.
A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis.
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DOI：
10.1038/s41467-022-35335-w
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发表时间：
2022-12-10
影响因子：
16.6
通讯作者：
Wang, Yong-Xu
中科院分区：
文献类型：
--
作者：
Chen, Qingbo;Huang, Lei;Pan, Dongning;Hu, Kai;Li, Rui;Friedline, Randall H.;Kim, Jason K.;Zhu, Lihua Julie;Guertin, David A.;Wang, Yong-Xu
脂肪产热的信号机制尚未完全阐明。特别是，选择性表达在棕色脂肪组织（BAT）和米色脂肪细胞的脂肪因子的参与仍有待研究。在这里，我们表明，以前未表征的脂肪因子（UPF 0687蛋白/人C20 orf 27同源物），我们命名为Adissp（脂肪分泌信号蛋白）是一个关键的调节白色脂肪组织（WAT）产热和葡萄糖稳态。Adissp的表达是脂肪特异性的，并且高度富集BAT，其分泌受β3肾上腺素能激活的刺激。功能获得研究共同表明，分泌型Adissp促进WAT产热，改善葡萄糖稳态，并防止肥胖。脂肪特异性Adissp基因敲除小鼠在WAT布朗宁方面存在缺陷，并且易受高脂肪饮食诱导的肥胖和高血糖症的影响。Adissp与脂肪细胞表面的一个假定受体结合，激活蛋白激酶A，而不依赖于β-肾上腺素能信号传导。这些结果确立了BAT富集的Adissp作为产热过程中的主要上游信号组分，并为治疗肥胖和糖尿病提供了潜在途径。调节脂肪产热的信号机制尚未完全阐明。在这里，作者表明，富含棕色脂肪的脂肪因子ADISSP促进脂肪产热，改善代谢健康，而不依赖于β-肾上腺素能受体。
The signaling mechanisms underlying adipose thermogenesis have not been fully elucidated. Particularly, the involvement of adipokines that are selectively expressed in brown adipose tissue (BAT) and beige adipocytes remains to be investigated. Here we show that a previously uncharacterized adipokine (UPF0687 protein / human C20orf27 homolog) we named as Adissp (Adipose-secreted signaling protein) is a key regulator for white adipose tissue (WAT) thermogenesis and glucose homeostasis. Adissp expression is adipose-specific and highly BAT-enriched, and its secretion is stimulated by β3-adrenergic activation. Gain-of-functional studies collectively showed that secreted Adissp promotes WAT thermogenesis, improves glucose homeostasis, and protects against obesity. Adipose-specific Adissp knockout mice are defective in WAT browning, and are susceptible to high fat diet-induced obesity and hyperglycemia. Mechanistically, Adissp binds to a putative receptor on adipocyte surface and activates protein kinase A independently of β-adrenergic signaling. These results establish BAT-enriched Adissp as a major upstream signaling component in thermogenesis and offer a potential avenue for the treatment of obesity and diabetes. The signaling mechanisms regulating adipose thermogenesis have not been fully elucidated. Here, the authors show that a brown fat-enriched adipokine ADISSP promotes adipose thermogenesis and improves metabolic health independently of b-adrenergic receptor.
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